TUBB2B encodes tubulin beta 2B, a β-tubulin isoform that is a major structural constituent of microtubules 1. Functionally, TUBB2B forms GTP-bound heterodimers with α-tubulin that polymerize to build microtubule structures, with GTP hydrolysis regulating microtubule dynamics 1. TUBB2B plays a critical role in axon guidance and neuronal migration during brain development 12. Mutations in TUBB2B cause tubulinopathies, a group of neurodevelopmental disorders characterized by complex cortical malformations 3. Pathogenic variants lead to defects in neuronal migration and lamination, resulting in lissencephaly, microlissencephaly, polymicrogyria, and associated abnormalities including microcephaly, basal ganglia dysmorphism, and corpus callosum dysgenesis 34. TUBB2B mutations are among the most frequently identified causes of polymicrogyria, the most common cortical malformation 5. Disease mechanisms involve altered microtubule dynamics through disrupted GTP binding, impaired protofilament interactions, and defective motor protein engagement 3. Beyond neurodevelopmental roles, TUBB2B is overexpressed in triple-negative breast cancer and hepatocellular carcinoma, where it promotes tumor progression and metastatic colonization through interactions with translational machinery and cholesterol metabolism pathways 67. Prenatal diagnosis of TUBB2B-associated tubulinopathies is possible via ultrasound and fetal MRI, facilitating counseling and prognostication 89.